[ 18 F ] MK ‐9470 PET measurement of cannabinoid CB 1 receptor availability in chronic cannabis users

Δ 9 ‐Tetrahydrocannabinol, the main psychoactive component of cannabis, exerts its central effects through activation of the cerebral type 1 cannabinoid ( CB 1 ) receptor. Pre‐clinical studies have provided evidence that chronic cannabis exposure is linked to decreased CB 1 receptor expression and this is thought to be a component underlying drug tolerance and dependence. In this study, we make first use of the selective high‐affinity positron emission tomography ( PET ) ligand [ 18 F ] MK ‐9470 to obtain in vivo measurements of cerebral CB 1 receptor availability in 10 chronic cannabis users (age = 26.0 ± 4.1 years). Each patient underwent [ 18 F ] MK ‐9470 PET within the first week following the last cannabis consumption. A population of 10 age‐matched healthy subjects (age = 23.0 ± 2.9 years) was used as control group. Parametric modified standardized uptake value images, reflecting CB 1 receptor availability, were calculated. Statistical parametric mapping and volume‐of‐interest ( VOI ) analyses of CB 1 receptor availability were performed. Compared with controls, cannabis users showed a global decrease in CB 1 receptor availability (−11.7 percent). VOI ‐based analysis demonstrated that the CB 1 receptor decrease was significant in the temporal lobe (−12.7 percent), anterior (−12.6 percent) and posterior cingulate cortex (−13.5 percent) and nucleus accumbens (−11.2 percent). Voxel‐based analysis confirmed this decrease and regional pattern in CB 1 receptor availability in cannabis users. These findings revealed that chronic cannabis use may alter specific regional CB 1 receptor expression through neuroadaptive changes in CB 1 receptor availability, opening the way for the examination of specific CB 1 ‐cannabis addiction interactions which may predict future cannabis‐related treatment outcome.